Abstract
Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really beneficial. However, the development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly associated with the development of recurrence (P= 0.01) and indicated poor survival in patients of Dukes' classes B and C, in which most recurrences (82%) occurred. An increased rate of tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies. © 1999 Cancer Research Campaign
Keywords: chromosome 18, colorectal cancer, loss of heterozygosity, prognosis
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- Arveux I., Boutron M. C., El Mrini T., Arveux P., Liabeuf A., Pfitzenmeyer P., Faivre J. Colon cancer in the elderly: evidence for major improvements in health care and survival. Br J Cancer. 1997;76(7):963–967. doi: 10.1038/bjc.1997.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cawkwell L., Bell S. M., Lewis F. A., Dixon M. F., Taylor G. R., Quirke P. Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology. Br J Cancer. 1993 Jun;67(6):1262–1267. doi: 10.1038/bjc.1993.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
- Elo J. P., Kvist L., Leinonen K., Isomaa V., Henttu P., Lukkarinen O., Vihko P. Mutated human androgen receptor gene detected in a prostatic cancer patient is also activated by estradiol. J Clin Endocrinol Metab. 1995 Dec;80(12):3494–3500. doi: 10.1210/jcem.80.12.8530589. [DOI] [PubMed] [Google Scholar]
- Eppert K., Scherer S. W., Ozcelik H., Pirone R., Hoodless P., Kim H., Tsui L. C., Bapat B., Gallinger S., Andrulis I. L. MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell. 1996 Aug 23;86(4):543–552. doi: 10.1016/s0092-8674(00)80128-2. [DOI] [PubMed] [Google Scholar]
- Fearon E. R., Cho K. R., Nigro J. M., Kern S. E., Simons J. W., Ruppert J. M., Hamilton S. R., Preisinger A. C., Thomas G., Kinzler K. W. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. doi: 10.1126/science.2294591. [DOI] [PubMed] [Google Scholar]
- Fielding L. P., Hittinger R., Grace R. H., Fry J. S. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Lancet. 1992 Aug 29;340(8818):502–506. doi: 10.1016/0140-6736(92)91708-g. [DOI] [PubMed] [Google Scholar]
- Frank C. J., McClatchey K. D., Devaney K. O., Carey T. E. Evidence that loss of chromosome 18q is associated with tumor progression. Cancer Res. 1997 Mar 1;57(5):824–827. [PubMed] [Google Scholar]
- Hedrick L., Cho K. R., Fearon E. R., Wu T. C., Kinzler K. W., Vogelstein B. The DCC gene product in cellular differentiation and colorectal tumorigenesis. Genes Dev. 1994 May 15;8(10):1174–1183. doi: 10.1101/gad.8.10.1174. [DOI] [PubMed] [Google Scholar]
- Iino H., Fukayama M., Maeda Y., Koike M., Mori T., Takahashi T., Kikuchi-Yanoshita R., Miyaki M., Mizuno S., Watanabe S. Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q, and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential. Cancer. 1994 Mar 1;73(5):1324–1331. doi: 10.1002/1097-0142(19940301)73:5<1324::aid-cncr2820730503>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
- Jen J., Kim H., Piantadosi S., Liu Z. F., Levitt R. C., Sistonen P., Kinzler K. W., Vogelstein B., Hamilton S. R. Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med. 1994 Jul 28;331(4):213–221. doi: 10.1056/NEJM199407283310401. [DOI] [PubMed] [Google Scholar]
- Jernvall P., Mäkinen M., Karttunen T., Mäkelä J., Vihko P. Conserved region mutations of the p53 gene are concentrated in distal colorectal cancers. Int J Cancer. 1997 Feb 20;74(1):97–101. doi: 10.1002/(sici)1097-0215(19970220)74:1<97::aid-ijc17>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- Kato M., Ito Y., Kobayashi S., Isono K. Detection of DCC and Ki-ras gene alterations in colorectal carcinoma tissue as prognostic markers for liver metastatic recurrence. Cancer. 1996 Apr 15;77(8 Suppl):1729–1735. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1729::AID-CNCR47>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
- Kikuchi-Yanoshita R., Konishi M., Fukunari H., Tanaka K., Miyaki M. Loss of expression of the DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial adenomatous polyposis patients. Cancer Res. 1992 Jul 1;52(13):3801–3803. [PubMed] [Google Scholar]
- Mäkelä J. T., Laitinen S. O., Kairaluoma M. I. Five-year follow-up after radical surgery for colorectal cancer. Results of a prospective randomized trial. Arch Surg. 1995 Oct;130(10):1062–1067. doi: 10.1001/archsurg.1995.01430100040009. [DOI] [PubMed] [Google Scholar]
- O'Connell M. J., Schaid D. J., Ganju V., Cunningham J., Kovach J. S., Thibodeau S. N. Current status of adjuvant chemotherapy for colorectal cancer. Can molecular markers play a role in predicting prognosis? Cancer. 1992 Sep 15;70(6 Suppl):1732–1739. doi: 10.1002/1097-0142(19920915)70:4+<1732::aid-cncr2820701614>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Obrand D. I., Gordon P. H. Incidence and patterns of recurrence following curative resection for colorectal carcinoma. Dis Colon Rectum. 1997 Jan;40(1):15–24. doi: 10.1007/BF02055676. [DOI] [PubMed] [Google Scholar]
- Ponz de Leon M., Sant M., Micheli A., Sacchetti C., Di Gregorio C., Fante R., Zanghieri G., Melotti G., Gatta G. Clinical and pathologic prognostic indicators in colorectal cancer. A population-based study. Cancer. 1992 Feb 1;69(3):626–635. doi: 10.1002/1097-0142(19920201)69:3<626::aid-cncr2820690305>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Sant M., Capocaccia R., Verdecchia A., Gatta G., Micheli A., Mariotto A., Hakulinen T., Berrino F. Comparisons of colon-cancer survival among European countries: The Eurocare Study. Int J Cancer. 1995 Sep 27;63(1):43–48. doi: 10.1002/ijc.2910630109. [DOI] [PubMed] [Google Scholar]
- Thiagalingam S., Lengauer C., Leach F. S., Schutte M., Hahn S. A., Overhauser J., Willson J. K., Markowitz S., Hamilton S. R., Kern S. E. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet. 1996 Jul;13(3):343–346. doi: 10.1038/ng0796-343. [DOI] [PubMed] [Google Scholar]
- Turnbull R. B., Jr, Kyle K., Watson F. R., Spratt J. Cancer of the colon: the influence of the no-touch isolation technic on survival rates. Ann Surg. 1967 Sep;166(3):420–427. doi: 10.1097/00000658-196709000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vernava A. M., 3rd, Longo W. E., Virgo K. S., Coplin M. A., Wade T. P., Johnson F. E. Current follow-up strategies after resection of colon cancer. Results of a survey of members of the American Society of Colon and Rectal Surgeons. Dis Colon Rectum. 1994 Jun;37(6):573–583. doi: 10.1007/BF02050993. [DOI] [PubMed] [Google Scholar]